Osmotic systems manufactured in the form of osmotic devices for delivering a drug to an environment of use are known to the art in U.S. Pat. Nos. 3,845,770 and 3,916,899, both issued to inventors Felix Theeuwes and Takeru Higuchi. A typical system, disclosed in these patents, comprises a semipermeable wall that surrounds a compartment containing a drug. The wall is permeable to an external fluid and substantially impermeable to the passage of drug. There is a passageway through the wall for delivering drug from the system. The system releases drug by fluid being continuously imbibed through the wall into the compartment at a rate determined by the permeability of the wall and the osmotic pressure gradient across the wall to produce a solution containing soluble drug that is dispensed from the system over time.
While the above system is an outstanding invention and represents a pioneer advancement in the delivery art, and while it is endowed with ideal delivery kinetics useful for delivering numerous beneficial drugs at controlled rates and continuously to the environment of use, there is an occasional instance where the delivery kinetics of the system can be unexpectedly improved leading to more desirable results. For example, many antiinflammatory drugs are practically insoluble in acid environments, such as in the gastric fluid of the stomach, and these drugs on their delivery from the system immediately precipitate on contact with the gastric fluid. This phenonemon occurs with precipitating drug accumulating at the exit of the passageway and on the exterior surface of the wall of the system. The precipitated drug impedes the flow of a saturated drug solution through the passageway, and the precipitated drug on the wall also impedes the imbibition of fluid into the system. These phenomena seriously diminish the release of these drugs at meaningful and beneficial rates from the system.
In U.S. Pat. No. 4,036,228, issued to Felix Theeuwes, the patentee discloses an osmotic system embodying a means for delivering drugs that are hard to deliver, particularly drugs that are practically insoluble in aqueous-type fluids. The means consists essentially in charging the system with an effervescent couple comprising an acidic component and a basic component. In operation when the system is in a fluid environment, the couple imbibes fluid into the system, thereby wetting the couple, causing it to react and produce in the system an effervescent solution. The effervescent solution creates a neutral condition in the system and it dispenses the drug from the system. The patent does not address itself to the delivery of drugs that exhibit limited solubilities in acidic environments, the use of only the basic components, and the production of effervescence in the environment of use.
Thus, in the light of the above discussion, it will be readily appreciated by those versed in the subject art that a critical need exists for a means for delivering drugs that have limited solubilities in acidic environments, especially where the means overcomes the tribulations associated with the prior art. Likewise, it will be further appreciated by those skilled in the art, that if a novel and useful method is made available for delivering these drugs, such a method would have a positive value and also represent a substantial contribution to the art.